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半夏泻心汤通过调节STAT3信号通路和肠道微生物群抑制结肠炎相关结直肠癌的发展。

Banxia Xiexin Decoction inhibits colitis-associated colorectal cancer development by modulating STAT3 signaling and gut microbiota.

作者信息

Yue Yinzi, Su Lianlin, Wang Yahui, Li Xiaoman, Xiao Xiaoyan, Xie Jin, Yan Shuai

机构信息

Department of General Surgery, Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou 215009, China.

School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.

出版信息

Chin Herb Med. 2024 May 21;17(2):380-391. doi: 10.1016/j.chmed.2024.02.004. eCollection 2025 Apr.

DOI:10.1016/j.chmed.2024.02.004
PMID:40256716
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12009064/
Abstract

OBJECTIVE: To investigate the therapeutic effects of Banxia Xiexin Decoction (BXD), a herbal medicine formula, on inflammation and the imbalance of the gut microbiota in a rat model of colorectal cancer (CRC) induced by azoxymethane (AOM) /dextran sulfate sodium (DSS). METHODS: A total of 75 male C57BL/6 mice were randomly divided into five groups: normal control group (NC), model group (MODEL), low-dose BXD treatment group (L-BXD), high-dose BXD treatment (H-BXD) group and MS treatment group (MS). BXD and MS were used in CRC mice at the doses of 3.915 g/kg, 15.66 g/kg, 0.6 g/kg for 3 weeks consecutively. Histopathological changes in the colon were observed using hematoxylin-eosin (HE) staining. The content of inflammatory factors in serum was detected by an enzyme-linked immunosorbent assay (ELISA), and the expression of mRNA and protein of genes related to immunity, apoptosis, inflammation, and inflammatory factors was evaluated. Changes in the intestinal flora of mouse fecal were determined based on high-throughput sequencing of the 16S rRNA microbial gene. RESULTS: Compared to the model group, the low-dose BXD and high-dose BXD groups decreased the number of colon tumors, reversed weight loss, and shortened colon length of mice. The pathological examination showed that BXD alleviated the malignancy of intestinal tumors. It also suppressed signal transducer and activator of transcription 3 (STAT3), matrix metalloproteinase-9 (MMP-9), and transforming growth factor beta 1 (TGF-β1) expression, while increasing the expression of the tight junction protein ZO-1 in colon tissues. Additionally, the levels of key pathway proteins involved in inflammation (phosphorylated-STAT3, Bcl-2, COX-2) and cell cycle regulatory molecules (c-Myc and PCNA) were reduced. According to 16S rRNA sequence analysis, BXD enhanced the relative abundance of potentially beneficial bacteria, while that of cancer-related bacteria decreased. CONCLUSION: BXD plays a preventive role in developing colorectal cancer; its mechanisms are related to the inhibition of inflammation and tumor proliferation, as well as maintenance of intestinal homeostasis.

摘要

目的：探讨中药方剂半夏泻心汤（BXD）对氧化偶氮甲烷（AOM）/葡聚糖硫酸钠（DSS）诱导的大鼠结直肠癌（CRC）模型炎症及肠道微生物群失衡的治疗作用。 方法：将75只雄性C57BL/6小鼠随机分为五组：正常对照组（NC）、模型组（MODEL）、低剂量BXD治疗组（L-BXD）、高剂量BXD治疗组（H-BXD）和甲磺酸伊马替尼治疗组（MS）。BXD和MS以3.915 g/kg、15.66 g/kg、0.6 g/kg的剂量连续3周用于CRC小鼠。采用苏木精-伊红（HE）染色观察结肠组织病理学变化。采用酶联免疫吸附试验（ELISA）检测血清中炎症因子含量，并评估免疫、凋亡、炎症及炎症因子相关基因的mRNA和蛋白表达。基于16S rRNA微生物基因的高通量测序确定小鼠粪便肠道菌群的变化。 结果：与模型组相比，低剂量BXD组和高剂量BXD组降低了小鼠结肠肿瘤数量，逆转了体重减轻，并缩短了结肠长度。病理检查显示，BXD减轻了肠道肿瘤的恶性程度。它还抑制信号转导和转录激活因子3（STAT3）、基质金属蛋白酶-9（MMP-9）和转化生长因子β1（TGF-β1）的表达，同时增加结肠组织中紧密连接蛋白ZO-1的表达。此外，炎症相关关键通路蛋白（磷酸化STAT3、Bcl-2、COX-2）和细胞周期调节分子（c-Myc和PCNA）的水平降低。根据16S rRNA序列分析，BXD提高了潜在有益菌的相对丰度，而与癌症相关菌的相对丰度降低。 结论：BXD对结直肠癌的发生具有预防作用；其机制与抑制炎症和肿瘤增殖以及维持肠道稳态有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12c8/12009064/eacdf9676ef7/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12c8/12009064/386d49933735/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12c8/12009064/6fbbbdc1d743/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12c8/12009064/e5b0cf3338c7/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12c8/12009064/2042a7f7bcdf/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12c8/12009064/dd8404c6b59f/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12c8/12009064/f92ad9952b7a/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12c8/12009064/967b9abc8651/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12c8/12009064/eacdf9676ef7/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12c8/12009064/386d49933735/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12c8/12009064/6fbbbdc1d743/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12c8/12009064/e5b0cf3338c7/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12c8/12009064/2042a7f7bcdf/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12c8/12009064/dd8404c6b59f/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12c8/12009064/f92ad9952b7a/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12c8/12009064/967b9abc8651/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12c8/12009064/eacdf9676ef7/gr8.jpg

相似文献

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引用本文的文献

[1]
Qingjie Fuzheng Granule prevents colitis-associated colorectal cancer by inhibiting abnormal activation of NOD2/NF-B signaling pathway mediated by gut microbiota disorder.

Chin Herb Med. 2025-4-3

本文引用的文献

[1]
Modulation of tumor-associated macrophages in colitis-associated colorectal cancer.

J Cell Physiol. 2022-12

[2]
Colorectal Cancer: Preoperative Evaluation and Staging.

Surg Oncol Clin N Am. 2022-4

[3]
Bioactive components of Banxia Xiexin Decoction for the treatment of gastrointestinal diseases based on flavor-oriented analysis.

J Ethnopharmacol. 2022-6-12

[4]
A comprehensive framework for early-onset colorectal cancer research.

Lancet Oncol. 2022-3

[5]
High-Fat Diet Promotes Colorectal Tumorigenesis Through Modulating Gut Microbiota and Metabolites.

Gastroenterology. 2022-1

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Genes Dev. 2021-6

[7]
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Gastroenterology. 2021-8

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BMC Cancer. 2021-4-6

[9]
Emu Oil and Saireito in combination reduce tumour development and clinical indicators of disease in a mouse model of colitis-associated colorectal cancer.

Biomed Pharmacother. 2021-6

[10]
Efficacy of modified Banxia Xiexin decoction in the management of Wei-Pi syndrome (postprandial distress syndrome): study protocol for a randomized, waitlist-controlled trial.

Trials. 2021-2-12

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